Article Text
Abstract
Background CRTH2 antagonism has been shown to reduce eosinophilic airway inflammation and improve lung function in patients with severe eosinophilic asthma. To better understand the role of CRTH2 in the pathogenesis of this asthma phenotype, we have carried out a cross-sectional study to investigate the CRTH2 positive cell counts in peripheral blood of patients with severe eosinophilic asthma.
Methods Blood was taken from 12 controls and 33 patients with asthma, 21 of whom met the 2014 ERS/ATS guideline criteria for severe asthma and had historical evidence of eosinophilic airway inflammation as defined before (Pavord et al. Lancet 2012;380:651–9). Th2 were detected as CD3+CD4+CRTH2+, Tc2 as CD3+CD8+CRTH2+, eosinophils as SSChighCRTH2+, and basophils as CD123+CRTH2+ by flow cytometry, and numbers presented as total cell counts in peripheral blood. Data were analysed using one-way ANOVA followed by the Newman-Keuls test.
Results CRTH2 cell counts were reasonably repeatable within patients (ICC 0.84; n = 9). Mean ± SD CRTH2+ cell counts were 168 ± 81, 322 ± 191, 710 ± 322 and 290 ± 179 × 106 cells/L in normal controls (n = 12), patients with mild to moderate asthma (n = 12), patients with severe asthma at BTS step 4 (n = 10), and patients with severe asthma at BTS step 5 (n = 11) respectively (Figure 1). Most CRTH2 + cells were eosinophils (Figure 1).
Conclusion Blood CRTH2+ cells are increased in subjects with severe eosinophilic asthma, mainly because of increased CRTH2+ eosinophils. Eosinophils and basophils numbers are significantly increased in severe eosinophilic asthma at step 4 but not step 5. Th2 and Tc2 cell numbers are less clearly associated with severe asthma. CRTH2+ cell numbers are lower in patients treated with prednisolone.